The placebo effect and the autonomic nervous system: evidence for an intimate relationship

Philosophical Transactions of the Royal Society B: Biological Sciences, Jun 2011

For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of ‘implicit affordance’, which assumes that placebo effects are dependent on ‘lived experience’ rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects.

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The placebo effect and the autonomic nervous system: evidence for an intimate relationship

Karin Meissner 0 1 0 Institute of General Practice, Klinikum rechts der Isar, Technische Universita t , Orleansplatz 47, 81776 Munich , Germany 1 Institute of Medical Psychology, Ludwig-Maximilians-University , Goethestrasse 31, 80336 Munich , Germany For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of 'implicit affordance', which assumes that placebo effects are dependent on 'lived experience' rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects. 1. INTRODUCTION The last decade has seen an increased interest in the occurrence of placebo responses in various conditions. However, the vast majority of studies examine placebo effects in subjectively experienced outcomes, such as pain and depression. Relatively little is known about the capacity of placebo interventions to alter objectively assessed endpoints. Based on the meta-analyses of Hr objartsson & Gtzsche [1 4], a general view has arisen that placebo interventions do provide symptomatic relief but do not modify pathophysiologal processes underlying the disease. However, such a conclusion may be premature. For example, a subgroup analysis showed that physical outcome parameters modulated by the autonomic nervous system (ANS), such as gastric motility and lung function, improved in placebo-treated patients when compared with untreated controls [5]. Furthermore, the latest update of the meta-analysis of Hr objartsson & Gtzsche [4] showed a significant pooled placebo effect on lung function in asthma trials beyond regression-to-the-mean, although results still carried the risk of bias. Thus, there is some evidence from systematic reviews that parameters controlled by the ANS may be amenable to top-down modulation via placebo interventions. The ANS provides via elaborated afferent and efferent fibres a highly specific communication between the organs and the brain [6]. Therefore, the ANS is a likely candidate to mediate the effects of placebo interventions on end-organ functions. As will be shown below, the ANS also possesses a high functional specificity, which would even make it possible that organ-specific placebo effectsaccording to the suggestion givencan occur. This review will summarize the available evidence for placebo effects on organ functions that are controlled by the ANS. First, current psychological approaches to explain placebo effects are discussed, and a conceptual framework that can account for placebo effects on organ functions is provided. Second, the organization of the ANS, its afferent and efferent pathways and important relay stations in the brain are summarized. Third, a comprehensive review of studies examining placebo effects on autonomic organ functions will be presented, thereby focusing on the cardiovascular, the gastrointestinal and the pulmonary system. 2. HOW TO EXPLAIN PLACEBO EFFECTS ON AUTONOMIC FUNCTIONS Let us imagine a laboratory experiment aimed to investigate whether a placebo intervention can lower 1808 blood pressure, such as recently performed in our laboratory [7]. The participant, a male, healthy volunteer, was informed that he would receive one of three possible interventions: either a homoeopathic remedy to lower blood pressure or an identically looking placebo remedy in a double-blinded fashion or no remedy at all. After filling out some questionnaires, the experimenter asks him to sit in a comfortable chair and places a blood pressure cuff around his arm. The experimenter starts to measure blood pressure every 5 min and does not tell the participant about the results. After 30 min, the experimenter opens the randomization envelope, takes a pill out of a box and tells the participant that he would now receive a remedy that would either be a placebo drug or a homoeopathic drug, which will induce a measurable fall of blood pressure. The participant swallows the pill and the experimenter starts to measure blood pressure every 5 min for (...truncated)


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Karin Meissner. The placebo effect and the autonomic nervous system: evidence for an intimate relationship, Philosophical Transactions of the Royal Society B: Biological Sciences, 2011, pp. 1808-1817, 366/1572, DOI: 10.1098/rstb.2010.0403